Abstract

BACKGROUND:

This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years.

METHODS:

Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo.

RESULTS:

DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation.

Study design. Both groups of participants received a single challenge round of oral DMSA; those excreting significant heavy metals continued on to Phase 2, and received additional 6 additional rounds of DMSA or placebo.

Percentage change in urinary excretion of toxic metals. a: Percentage Change in Urinary Excretion of Toxic Metals after 1st and 9th Dose of DMSA in Phase 1. (n = 63). b: Percentage Change in Urinary Excretion of Toxic Metals after 1st and 9th dose of Round 1, and then 9th dose of Rounds 3, 5, and 7, for the group who received 7 rounds of DMSA. (n = 20).

RBC glucathione distributions. a: Initial RBC Glutathione Distribution (pre-treatment). Many autistic children have levels below and above the laboratory's reference range of 427-714 micromolar. Each histogram corresponds to the frequency between that value and 50 below it; ie, the histogram labelled "50" is the frequency of values from 0 to 50. b: RBC Glutathione Distribution 1-2 months after first round (3 days) of DMSA. The distribution has tightened dramatically, so that most children are within the laboratory's reference range for typical adults. c: Change in RBC glutathione 1-2 months after first round of DMSA. Children with initially low levels had a large increase in glutathione, and children with high levels had a large decrease, so that most levels of glutathione normalized. The black dots are the participants who received DMSA and glutathione lotion and the red dots are the participants who received DMSA and the placebo lotion. The trendlines for the two groups lie directly on top of one another, suggesting that the effect of the glutathione lotion is negligible compared to the effect of the DMSA.

Platelet count. a: Platelet Count before DMSA. Note many children have values above the reference range (130-450 k/mm3). One child had a very high value (1996 k/mm3) which is not shown on this chart. b: Platelet Count 1-2 months after first round of DMSA. The primary effect of DMSA is to decrease the elevated platelets, with little effect on those in the normal or low range. One child still had a very high value (1917 k/mm3) which is not shown on this chart. c: Platelet Count at End of Study. Both the 7-round and 1-round groups are plotted together, as the results were similar, although there was slightly more decrease for the 7-round than the 1-round group. The primary effect of DMSA is to normalize elevated or (in one case) low platelets. One child still has a high value of 1195 k/mm3 which is not shown, but it has decreased substantially from its initial value of 1996 k/mm3).